CAVIN1

Chr 17AR

caveolae associated protein 1

Also known as: CAVIN, CGL4, FKSG13, PTRF, cavin-1

NCBI Gene: 284119 ENSG00000177469 UniProt: Q6NZI2 OMIM: 603198

The protein is essential for caveolae formation and organization at the plasma membrane and promotes ribosomal RNA transcription by dissociating paused RNA polymerase I complexes. Mutations cause congenital generalized lipodystrophy type 4, a disorder characterized by generalized loss of adipose tissue and muscular dystrophy. The condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that enables the dissociation of paused ternary polymerase I transcription complexes from the 3' end of pre-rRNA transcripts. This protein regulates rRNA transcription by promoting the dissociation of transcription complexes and the reinitiation of polymerase I on nascent rRNA transcripts. This protein also localizes to caveolae at the plasma membrane and is thought to play a critical role in the formation of caveolae and the stabilization of caveolins. This protein translocates from caveolae to the cytoplasm after insulin stimulation. Caveolae contain truncated forms of this protein and may be the site of phosphorylation-dependent proteolysis. This protein is also thought to modify lipid metabolism and insulin-regulated gene expression. Mutations in this gene result in a disorder characterized by generalized lipodystrophy and muscular dystrophy. [provided by RefSeq, Nov 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.081 OMIM phenotype

Clinical Summary— CAVIN1

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Gene-Disease Validity (ClinGen)

lipodystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 95 VUS of 184 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.005

Z-score 1.40

OE 0.51 (0.27–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.38Z-score

OE missense 0.76 (0.67–0.85)

195 obs / 257.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.27–1.08)

0≤0.351.4

Missense OE?0.76 (0.67–0.85)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 5 / 9.7Missense obs/exp: 195 / 257.1Syn Z: 1.08

This gene — mechanism propensity

0.6065th %ile

GOF

0.78top 25%

LOF

0.4332th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

LOF100% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

184 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic6

VUS95

Likely Benign39

Benign21

Conflicting11

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	0	0	0	10
Likely Pathogenic	6	0	0	0	6
VUS	0	67	23	5	95
Likely Benign	0	2	17	20	39
Benign	0	0	20	1	21
Conflicting	—				11
Total	16	69	60	26	182

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

6 pathogenic / likely-pathogenic (of 7) ClinVar copy-number / structural variants overlap CAVIN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →